Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bulk RNAseq of control, XBP1-deficient or XBP1/IRE1-deficient cDC1s from subcutaneous B16- melanoma bearing mice

ABSTRACT: The unfolded protein response (UPR) sensor IRE1 and its target, the transcription factor XBP1s critically regulate the function of dendritic cell (DC) subtypes. However, the contribution of the IRE1/XBP1s axis in DCs to the antitumor immunity is not entirely understood. Here, using reporter mice we found that DCs, in particular type 1 conventional DCs (cDC1s), are major targets of IRE1 RNase activity in melanoma tumors. Deletion of XBP1s in CD11c+ cells resulted in augmented tumor growth, impaired effector T cell responses and decreased accumulation of TCF-1+CD8+ T cells with a precursor exhausted profile. Transcriptomic studies revealed that XBP1 deletion in tumor cDC1s induced regulated IRE1 dependent decay (RIDD) of mRNAs, which accounted for the dysregulated T cell immunity in melanoma. Thus, a strict regulatory circuit involving IRE1 RNase and XBP1s in DCs ensures optimal antitumor T cell immunity in melanoma models.

ORGANISM(S): Mus musculus

PROVIDER: GSE195439 | GEO | 2023/05/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Profiling gene expression in 32Dcl3 cells following Xbp1 retrovirus vector transfection

Project description:The significant changes of hematopoietic cells induced by Xbp1S expression indicate that there is global alteration in gene expression. UPR induces transcription of Xbp1, and phosphorylation of the ER transmembrane kinase IRE1 initiates UPR-mediated mRNA splicing of Xbp1, resulting in the production of Xbp1S, an active form of a basic leucine zipper transcription factor. In the present study, Xbp1S retrovirus vector infected 32cl3 cells show cell cycle arrest and myeloid differentiation. Xbp1S may modulate important genes of differentiation and the cell cycle. RNA samples extracted from 32Dcl3 cells with pMIG (empty vector), pMY-Xbp1U (unspliced form) and pMY-Xbp1S (spliced form) retroviral vector transfected cells were subjected to expression profiling using the Affymetrix GeneChip microarray system.

2010-10-01 | E-GEOD-17023 | biostudies-arrayexpress

MDA-MB-231 gene expression upon IRE1 RNase inhibition with MKC-8866

Project description:The IRE1 Rnase domain has been implicated in the pathology of triple negative breast cancer (TNBC), a disease with limited treatment options. The IRE1 Rnase mediates it's effects on the transcriptome via activation of the trancription factor XBP1s and via direct cleavage of mRNA through a process called RIDD. The processes through which the RNase domain contributes to TNBC is not fully understood. We used a novel small molecule inhibitor of the IRE1 Rnase to find novel targets of IRE1 in TNBC, in an effort to elucidate how it contributes to the disease.

2018-08-15 | GSE99766 | GEO

Contribution of the Unfolded Protein Response (UPR) transcription factor XBP1 to brain aging

Project description:In this project we aimed to evaluate the contribution of endoplasmic reticulum stress sensor IRE1 and its downstream transcription factor XBP1s to mammalian brain aging. We compared traits associated to aging at behavioral, electrophysiological, morphological and proteomic levels. We used transgenic animals overexpressing XBP1s in brain tissue and also wild type animals injected with adeno-associated virus to overexpress XBP1s in the brain during aging.

2022-11-04 | PXD020539 | Pride

Profiling gene expression in 32Dcl3 cells following Xbp1 retrovirus vector transfection

2010-10-01 | GSE17023 | GEO

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [RNA-Seq]

Project description:Dendritic cells (DCs) play critical roles in regulating the innate and adaptive immune responses, and have long been a major focus of cancer immunotherapy. Accumulating evidence suggests that conventional type 1 DC (cDC1s) excel in cross-presentation of exogenous antigens on MHC-I molecules, and induction of antitumor CD8+ T cell immunity; however, obtaining large numbers of cDC1s is difficult. The use of reprogramming and differentiation technology is advantageous for obtaining unlimited numbers of autologous cDC1s especially for therapeutic interventions where repeated vaccinations are required. However, generation of cDC1s from human induced pluripotent stem cells (iPSCs) remains elusive.

2022-02-09 | GSE193487 | GEO

Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling [scRNA-seq]

2022-02-09 | GSE193485 | GEO

Effect of neuron-specific spliced XBP1 (XBP1s) overexpression on gene expression in the mouse brain

Project description:One major component of cellular proteome resides in the endoplasmic reticulum (ER), the key organelle for protein biogenesis in the secretory pathway. Disruption of ER proteostasis leads to ER stress, which subsequently activates multiple adaptive stress response pathways, collectedly termed as the unfolded protein response (UPR). One UPR branch is mediated by IRE1(inositol-requiring enzyme 1). Activation of the IRE1 UPR branch generates a potent transcriptional factor: spliced X-box–binding protein-1 (XBP1s). Since activation of this UPR branch has been shown to be neuroprotective in brain ischemia/stroke, it is critical to identify the XBP1s-regulated genes in neurons in vivo and thus help determine the molecular mechanisms underlying the beneficial effects exerted by this UPR branch. In this study, we performed RNA-Seq analysis on the hippocampus from XBP1s conditional transgenic mice.

2022-10-22 | GSE160263 | GEO

Pharmacologic IRE1/XBP1s Activation Confers Targeted ER Proteostasis Reprogramming

Project description:Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. However, no pharmacologic activators of this pathway identified to date are suitable for ER proteostasis remodeling through selective activation of IRE1/XBP1s signaling. Here, we use high-throughput screening to identify non-toxic compounds that induce ER proteostasis remodeling through IRE1/XBP1s activation. We employ transcriptional profiling to stringently confirm that our prioritized compounds selectively activate IRE1/XBP1s signaling without activating other cellular stress-responsive signaling pathways. Furthermore, we demonstrate that our compounds improve ER proteostasis of destabilized variants of amyloid precursor protein (APP) through an IRE1-dependent mechanism and reduce APP-associated mitochondrial toxicity in cellular models. These results establish highly-selective IRE1 activating compounds that can be widely employed to define the functional importance of IRE1/XBP1s activity for ER proteostasis regulation in the context of health and disease.

2020-04-17 | GSE148802 | GEO

IRE1 inhibitor [RNA-seq]

Project description:The role of the unfolded protein response (UPR) in the cellular innate response to RSV infection is not fully understood. To better the genomic targets for the IRE1-XBP1 pathway, RNA seq was conducted on RSV-infected small airway cells in the absence or presence of RSV infection and in the absence or presence of a selective IRE1a RNAse inhibitor. We identified expression changes in ~3.2K genes; of these, 279 required IRE1 and were enriched in IL-10 signaling and cytokine signaling pathways. These data indicate that IRE1a-XBP1s regulates genes important in epithelial mesenchymal transition, hexosamine biosynthesis and anti-viral signaling.

2023-04-30 | GSE228327 | GEO

Effect of Flt3L and DNGR-1 on the biology of tumor-infiltrating type 1 dendritic cells

Project description:DNGR-1 is a dead cell-sensing receptor specifically expressed in type 1 conventional dendritic cells (cDC1s), but whether it plays a role in antitumor immunity remains unexplored. In our work we have explored the transcriptional profile of tumor-infiltrating cDC1s competent or deficient in DNGR-1,

2021-05-19 | GSE145534 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data